Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease.

Two Types of Variational Arteries' Courses From the Superior Mesenteric Artery to Supply the Splenic Flexure: Gross Anatomical Study.

BACKGROUND: Complete mesocolic excision with central vascular ligation is a standard method for managing colon cancer. However, there is no consensus on its procedure, especially for cancer in the splenic flexure of the transverse colon. This is because various types of variational arteries are distributed to the region, and their running course below and near the pancreas leads to difficulty in ligating the artery. OBJECTIVE: To clarify the arterial distribution to the splenic flexure of the transverse colon using cadavers. DESIGN: The arteries in the transverse mesocolon distributed to the colon were dissected in cadavers, and their route was quantitatively visualized using drawing software. SETTINGS: This study was conducted at the Department of Anatomy, Tokyo Medical University. PATIENTS: Sixty cadavers donated to Tokyo Medical University in 2017-2021 were used. MAIN OUTCOME MEASURES: The arterial courses to the splenic flexure of the transverse colon in the mesocolon and their patterns were evaluated. RESULTS: We found 34 variational arteries distributed to the splenic flexure of the transverse colon. Most originated from the superior mesenteric artery and the middle colic artery, with their typical course below the pancreas. We identified another arterial course, crossing the mesocolon away from the pancreas toward the splenic flexure of the transverse colon. Furthermore, the origin of these arteries was not behind the pancreas and can be found in the caudal region of the pancreas. LIMITATIONS: We cannot discuss how the arteries within the transverse mesocolon are observed by CT examination. CONCLUSIONS: This study showed 2 types of arterial courses (below the pancreas and within the mesocolon) toward the splenic flexure of the transverse colon for the first time. In the latter case, the complete mesocolic excision with central vascular ligation is likely performed more easily than in the former. See Video Abstract. DOS TIPOS DE RECORRIDO VARIACIONAL DE LA ARTERIA DESDE LA ARTERIA MESENTRICA SUPERIOR PARA IRRIGAR EL NGULO ESPLNICO ESTUDIO ANATMICO MACROSCPICO: ANTECEDENTES:La escisión mesocólica completa con ligadura vascular central es un método estándar para el cáncer de colon. Sin embargo, no hay consenso sobre su procedimiento, especialmente para el cáncer en el ángulo esplénico del colon transverso. Esto se debe a que varios tipos de arterias variacionales se distribuyen en la región, y su recorrido por debajo y cerca del páncreas dificulta la ligadura de la arteria.OBJETIVO:Este estudio tuvo como objetivo aclarar la distribución arterial al SF del colon transverso utilizando cadáveres.DISEÑO:Las arterias en el mesocolon transverso distribuidas al colon fueron disecadas en cadáveres, y su ruta fue visualizada cuantitativamente utilizando un software de dibujo.AJUSTES:Este estudio se realizó en el Departamento de Anatomía de la Universidad Médica de Tokio.PACIENTES:Se utilizaron sesenta cadáveres donados a la Universidad Médica de Tokio en 2017-2021.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron los cursos arteriales al ángulo esplénico del colon transverso en el mesocolon y sus patrones.RESULTADOS:Encontramos 34 arterias variacionales distribuidas al ángulo esplénico del colon transverso. La mayoría se originaron en la arteria mesentérica superior y la arteria cólica media, con su trayecto típico por debajo del páncreas. Identificamos otro curso arterial, cruzando el mesocolon alejándose del páncreas hacia el ángulo esplénico del colon transverso. Además, el origen de estas arterias no estaba detrás del páncreas y se pueden encontrar en la región caudal del páncreas.LIMITACIONES:No podemos discutir cómo se observan las arterias dentro del mesocolon transverso mediante un examen de tomografía computarizada.CONCLUSIONES:Este estudio mostró por primera vez dos tipos de trayectos arteriales (por debajo del páncreas y dentro del mesocolon) hacia el ángulo esplénico del colon transverso. En el último caso, es probable que la escisión mesocólica completa con ligadura vascular central se realice más fácilmente que en el primero. (Traducción-Dr. Aurian Garcia Gonzalez ).

Geriatric nutritional risk index after neoadjuvant chemoradiotherapy and survival in older patients with advanced rectal cancer.

PURPOSE: To investigate the clinical impact of malnutrition on the survival of older patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. METHODS: We investigated the clinical significance of the geriatric nutritional risk index (GNRI) in 237 patients aged over 60 years with clinical stage II/III rectal adenocarcinoma who were treated with neoadjuvant long-course chemoradiotherapy or total neoadjuvant therapy followed by radical resection from 2004 to 2017. Pre-treatment and post-treatment GNRI were evaluated, with patients split into low (< 98) and high (≥ 98) GNRI groups. The prognostic impact of pre-treatment and post-treatment GNRI levels on overall survival (OS), post-recurrence survival (PRS), and disease-free survival (DFS) was evaluated using univariate and multivariate analyses. RESULTS: Fifty-seven patients (24.1%) before neoadjuvant treatment and 94 patients (39.7%) after neoadjuvant treatment were categorized with low GNRI. Pre-treatment GNRI levels were not associated with OS (p = 0.80) or DFS (p = 0.70). Patients in the post-treatment low GNRI group had significantly poorer OS than those in the post-treatment high GNRI group (p = 0.0005). The multivariate analysis showed that post-treatment low GNRI levels were independently associated with poorer OS (hazard ratio, 3.06; 95% confidence interval, 1.55-6.05; p = 0.001). Although post-treatment GNRI levels were not associated with DFS (p = 0.24), among the 50 patients with recurrence, post-treatment low GNRI levels were associated with poorer PRS (p = 0.02). CONCLUSION: Post-treatment GNRI is a promising nutritional score associated with OS and PRS in patients over 60 years with advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Novel mobilization of the medial approach without changing the position for robotic right hemicolectomy.

Conventional laparoscopic or robotic surgery for right-sided colon cancer often requires intraoperative repositioning and removal of the bowel. Changing positions during robotic surgery can be troublesome and robotic removal of the small intestine carries a risk of unexpected injury because robotic devices have a strong grasping force and no sense of touch. Herein, we introduce a novel mobilization of the medial approach without changing the position for robotic right hemicolectomy. Using this technique, mobilization is performed in counterclockwise succession, allowing all mobilizations and bowel removal to be completed sequentially, without positional change.

Advantages of the umbilical minilaparotomy-first approach in robotic rectal cancer surgery.

BACKGROUND: Since 2018, we have performed robotic rectal cancer surgery at our institution via the umbilical mini-laparotomy-first approach. In the present technical note, we introduce the advantages of this approach. METHODS: In this approach, a 3-cm mini-laparotomy and the wound protector attachment are performed prior to port placement for the da Vinci® Xi system. During robotic surgery, the assistant can adjust the location of the camera port within the wound protector. RESULTS: This approach is only different from the standard port placement in terms of the timing of minilaparotomy; therefore, there is no additional cost. This approach has several advantages. 1: Intraabdominal adhesion around the umbilicus can be dissected under direct vision. 2: Robot arm collision can be diminished. 3: The diverting stoma can be located just at the preoperative stoma-site marking. 4: The da Vinci® camera is less likely to be dirty. 5: Assistant ports can be added through the wound protector. However, sometimes interference between the wound protector extends inside the abdomen and other ports can be a problem, especially in small patients. A smaller-size wound protector is thus recommended in such cases. CONCLUSIONS: The umbilical minilaparotomy-first approach in robotic rectal cancer surgery is a simple and feasible technique with great advantages for not only ensuring successful robotic surgery but also reducing the stoma-associated complications.

Exacerbation of non-steroidal anti-inflammatory drug-induced enteropathy in C-C chemokine receptor type 7-deficient mice.

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) induce intestinal enteropathy and the pathophysiology is related to immune-mediated mechanisms. We aimed to investigate the role of C-C chemokine receptor type 7 (CCR7) which regulates immune cell migration in NSAID-induced enteropathy. METHODS: Injury of the small intestine was evaluated 24 h after the subcutaneous injection of indomethacin in CCR7-deficient (Ccr7-/- ) and wild-type (WT) mice. The cellular profile and cytokine production in intestinal cells were analyzed. Indomethacin-induced enteropathy was evaluated in mice adoptively transferred with CD103+ dendritic cells (DCs) from Ccr7-/- or WT mice. RESULTS: Indomethacin induced more severe intestinal injury in Ccr7-/- mice than in WT mice. The major inflammatory cytokines were not increased and the proportion of regulatory T cells following indomethacin injection was not decreased in Ccr7-/- mice compared with WT mice. The expression of interleukin (IL)-22 binding protein (IL-22BP), which inhibits IL-22 activity, was significantly higher in CD103+ DCs from Ccr7-/- mice than those from WT mice. Mice adoptively transferred with CD103+ DCs isolated from Ccr7-/- mice exhibited more severe intestinal injury following indomethacin injection compared with those adoptively transferred with CD103+ DCs of WT mice. Ccr7-/- mice injected with indomethacin showed a significant reduction in regenerating islet-derived 1 (Reg1) mRNA expression, which is regulated by IL-22, in intestinal epithelial cells. CONCLUSIONS: C-C chemokine receptor type 7 deficiency exacerbated NSAID-induced enteropathy in association with an altered phenotype of CD103+ DCs that produces IL-22BP. CCR7 contributes to protect the small intestine from NSAID-induced mucosal injury.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma.

BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Use of a convolutional neural network for classifying microvessels of superficial esophageal squamous cell carcinomas.

BACKGROUND AND AIM: The morphological diagnosis of microvessels on the surface of superficial esophageal squamous cell carcinomas using magnifying endoscopy with narrow-band imaging is widely used in clinical practice. Nevertheless, inconsistency, even among experts, remains a problem. We constructed a convolutional neural network-based computer-aided diagnosis system to classify the microvessels of superficial esophageal squamous cell carcinomas and evaluated its diagnostic performance. METHODS: In this retrospective study, a cropped magnifying endoscopy with narrow-band images from superficial esophageal squamous cell carcinoma lesions was used as the dataset. All images were assessed by three experts, and classified into three classes, Type B1, B2, and B3, based on the Japan Esophagus Society classification. The dataset was divided into training and validation datasets. A convolutional neural network model (ResNeXt-101) was trained and tuned with the training dataset. To evaluate diagnostic accuracy, the validation dataset was assessed by the computer-aided diagnosis system and eight endoscopists. RESULTS: In total, 1777 and 747 cropped images (total, 393 lesions) were included in the training and validation datasets, respectively. The diagnosis system took 20.3 s to evaluate the 747 images in the validation dataset. The microvessel classification accuracy of the computer-aided diagnosis system was 84.2%, which was higher than the average of the eight endoscopists (77.8%, P < 0.001). The area under the receiver operating characteristic curves for diagnosing Type B1, B2, and B3 vessels were 0.969, 0.948, and 0.973, respectively. CONCLUSIONS: The computer-aided diagnosis system showed remarkable performance in the classification of microvessels on superficial esophageal squamous cell carcinomas.

Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. METHODS: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6-12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios. RESULTS: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06-1.71], P = 0.015). The heterogeneity among studies was low (I2  = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. CONCLUSION: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.

Novel mass spectrometry-based comprehensive lipidomic analysis of plasma from patients with inflammatory bowel disease.

BACKGROUND AND AIM: Lipids play important roles in inflammation and may be involved in the pathophysiology of inflammatory bowel disease (IBD). Here, we evaluated the characteristics of the plasma lipid profile in patients with IBD. METHODS: Plasma samples were collected from 20 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC), and 10 healthy volunteers (HVs) after overnight fasting. The subjects were men between 20 and 49 years of age with no history of hyperlipidemia. A total of 698 molecular species in 22 lipid classes were analyzed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Lipid classes of lysophosphatidic acid, lysophosphatidylserine (LPS), phosphatidylserine (PS), and shingosine-1-phosphate (S1P) were significantly increased in UC patients compared with the HV. The LPS, PS, and S1P levels were significantly increased, while those of lysophosphatidylinositol and phosphatidylcholine were significantly decreased in CD patients compared with HV. Among PS species, the levels of PSacyl (PSa) 40:3, PSa 38:3, and PSa 42:4 were significantly higher in CD patients, both active and remissive stage, than in HV. The LPS 18:0 level was significantly higher in CD and UC patients compared with HV. PSa 40:3 and PSa 38:3 levels positively correlated with the Crohn's Disease Activity Index, erythrocyte sedimentation rate, and platelet count and negatively correlated with hemoglobin, hematocrit, and albumin levels in CD patients. CONCLUSION: The lipid profile in IBD patients exhibits significant alterations, and PS levels are associated with clinical disease activity in CD patients.

Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis.

BACKGROUND AND AIM: Galectin-1 plays a protective role against colitis by binding with polylactosamine structures on macrophages in ß-1,4-galactosyltransferase I-deficient mice, but the precise function of galectin-1 remains unknown. In the present study, we investigated the anti-inflammatory role of galectin-1 on macrophages to ameliorate ulcerative colitis in both animal model and human tissue samples. METHODS: The expression of galectin-1 in colonic tissues of ulcerative colitis patients was evaluated by immunohistochemistry. Cytokine production of mouse bone marrow-derived macrophages (BMDMs) cultured with galectin-1 was investigated. Galectin-1 binding capacity and polylactosamine expression in macrophages stimulated with lipopolysaccharides were evaluated by flow cytometry. BMDMs cultured with galectin-1 were transferred into Recombination activating gene (Rag) 2-/- mice, and the severity of the dextran sodium sulfate-induced colitis model was investigated. Furthermore, RNA sequencing was performed to characterize macrophages treated with galectin-1. RESULTS: In ulcerative colitis patients, tissue expression of galectin-1was decreased in inflamed mucosa compared with non-inflamed mucosa. Galectin-1 induced interleukin-10 production in BMDMs, and the interleukin-10 production was abrogated by lactose, which inhibits the interaction of oligosaccharide-galectin binding. Dextran sodium sulfate colitis was significantly ameliorated in Rag2-/- mice undergoing galectin-1-treated BMDM transfer compared with those undergoing vehicle-treated BMDM transfer. RNA sequencing revealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein ß and CD163, but decreased the expression of CD80 on BMDMs. CONCLUSION: Galectin-1, whose expression is decreased in the inflamed mucosa of ulcerative colitis patients, can ameliorate murine colitis by conferring oligosaccharide-dependent anti-inflammatory properties to macrophages.

Distinct Clinical Factors in Hospitalized Patients with Diverticular Bleeding and Diverticulitis.

BACKGROUND/AIMS: It is unclear why colonic diverticular bleeding and diverticulitis rarely coexist. This study compared the characteristics of these conditions. METHODS: This single-center retrospective study examined 310 consecutive patients hospitalized with an episode of diverticular disease (cases) and outpatients without a diverticular episode (controls) from January 2012 to December 2015. We investigated distinct clinical factors in hospitalized patients with diverticular bleeding and diverticulitis. RESULTS: We identified 183 patients with 263 episodes of diverticular bleeding and 127 patients with 135 episodes of diverticulitis during the study period. Patients with diverticular bleeding were significantly older than those with diverticulitis (median age 76 vs. 56 years) and had more cardiovascular disease, hypertension, diabetes, cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer performance status. Significantly more diverticular bleeding patients were taking antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and antiplatelet agent use (OR 7.29) were more significant risk factors for diverticular bleeding than for diverticulitis. CONCLUSIONS: Elderly people using antiplatelet drugs may be more susceptible to diverticular bleeding than diverticulitis.

Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study.

Background/Aims: Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC. Methods: This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed. Results: Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%-71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%-76.4%). One adverse event not related to budesonide rectal foam occurred. Conclusions: The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

Carbon dioxide insufflation reduces the relapse of ulcerative colitis after colonoscopy: A randomized controlled trial.

BACKGROUND AND AIM: Colonoscopy is necessary for diagnosing and surveilling patients with ulcerative colitis, though it may cause disease flares. Colonoscopy with carbon dioxide (CO2) insufflation decreases abdominal discomfort; however, its effect on exacerbation incidence in ulcerative colitis remains unclear. Therefore, this study aimed to evaluate the colonoscopy effects using CO2 insufflation in patients with ulcerative colitis. METHODS: Overall, 96 remissive patients with ulcerative colitis (partial Mayo score ≤ 2) who underwent total colonoscopy between March 2015 and December 2019 at Osaka University Hospital were enrolled and blindly randomized to the CO2 (n = 45) and air (n = 51) insufflation group (UMIN-CTR, number: UMIN000018801). The post-procedural abdominal discomfort and the clinical relapse (partial Mayo score ≥ 3) rate within 8 weeks were evaluated. RESULTS: Baseline backgrounds did not differ between the groups. The mean abdominal fullness and pain scores were significantly lower in the CO2 group than in the Air group immediately (p = 0.0003, p = 0.0003) and 30 min (p < 0.0001, p < 0.0001) after colonoscopy. While the overall clinical relapse rate remained unchanged between the groups, the clinical relapse rate at 8 weeks after colonoscopy was significantly lower in the CO2 group than in the Air group in patients not in complete remission (Mayo endoscopic subscore ≥ 1, p = 0.049; or partial Mayo score ≥ 1, p = 0.022). CONCLUSIONS: CO2 insufflation can reduce abdominal discomfort in remissive patients with ulcerative colitis and decrease clinical relapse at 8 weeks after colonoscopy for those not in complete remission.

Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Environmental factors are associated with onset and course of inflammatory bowel disease (IBD). Our previous study by about 1,100 IBD patients revealed half of the patients experienced seasonal exacerbation of disease. We investigated the seasonality of fecal microbiota composition of IBD patients. METHODS: Fecal samples were consecutively collected in each season from IBD outpatients and healthy controls between November 2015 and April 2019. Participants who were treated with full elemental diet or antibiotics within 6 months or had ostomates were excluded. Bacterial profiles were analyzed by 16S rRNA sequencing, and the changes between the diseases and seasons were compared. RESULTS: A total of 188 fecal samples were analyzed from 47 participants comprising 19 Crohn's disease (CD) patients, 20 ulcerative colitis (UC) patients, and 8 healthy controls (HC). In CD patients, the phylum Actinobacteria and TM7 were both significantly more abundant in autumn than in spring and winter, but not in UC patients and HC. Moreover, the genera Actinomyces, a member of Actinobacteria, and c_TM7-3;o_;f_;g_ (TM7-3), that of TM7, were significantly more abundant in autumn than in spring, and the abundance of Actinomyces was significantly correlated with that of TM7-3 throughout the year in CD patients, but not in UC patients and HC. CD patients with high abundance of TM7-3 in the autumn required significantly fewer therapeutic intervention than those without seasonal fluctuation. CONCLUSIONS: Oral commensals Actinomyces and its symbiont TM7-3 were correlatively fluctuated in the feces of CD patients by season, which could affect the disease course.

Lysophosphatidylserines derived from microbiota in Crohn's disease elicit pathological Th1 response.

Microbiota alteration and IFN-γ-producing CD4+ T cell overactivation are implicated in Crohn's disease (CD) pathogenesis. However, it remains unclear how dysbiosis enhances Th1 responses, leading to intestinal inflammation. Here, we identified key metabolites derived from dysbiotic microbiota that induce enhanced Th1 responses and exaggerate colitis in mouse models. Patients with CD showed elevated lysophosphatidylserine (LysoPS) concentration in their feces, accompanied by a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A. LysoPS induced metabolic reprogramming, thereby eliciting aberrant effector responses in both human and mouse IFN-γ-producing CD4+ T cells. Administration of LysoPS into two mouse colitis models promoted large intestinal inflammation. LysoPS-induced aggravation of colitis was impaired in mice lacking P2ry10 and P2ry10b, and their CD4+ T cells were hyporesponsive to LysoPS. Thus, our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota promote Th1-mediated intestinal pathology.

Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease.

The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25-0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26-0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Symptomatic hyponatremia: a rare but reversible adverse reaction of lubiprostone.

Several intestinal secretagogues became available for the patients with irritable bowel syndrome. We report a case of symptomatic hyponatremia after lubiprostone ingestion. A male patient was visiting our office to manage chronic kidney disease. He suffered chronic hepatitis (type C), which was successfully treated with asunaprevir and daclatasvir. He took lubiprostone due to constipation, and then watery diarrhoea was frequently developed. Next morning, he came to our hospital due to consciousness disturbance. Physical examination showed dehydration and laboratory data exhibited hyponatremia (110 mEq/L). Subsequent treatment against hypovolemic hyponatremia recovered his consciousness without any sequels. This case suggests that intestinal secretagogues can accompany severe electrolyte disturbance. Potential mechanisms for hyponatremia were discussed.

Narrow pelvic inlet plane area and obesity as risk factors for anastomotic leakage after intersphincteric resection.

BACKGROUND: Intersphincteric resection (ISR) has been increasingly used as the ultimate sphincter-preserving procedure in extremely low rectal cancer. The most critical complication of this technique is anastomotic leakage. The incidence rate of anastomotic leakage after ISR has been reported to range from 5.1% to 20%. AIM: To investigate risk factors for anastomotic leakage after ISR based on clinicopathological variables and pelvimetry. METHODS: This study was conducted at Department of Colorectal Surgery, Japanese Red Cross Medical Center, Tokyo, Japan, with a total of 117 patients. We enrolled 117 patients with extremely low rectal cancer who underwent laparotomic and laparoscopic ISRs at our hospital. We conducted retrospective univariate and multivariate regression analyses on 33 items to elucidate the risk factors for anastomotic leakage after ISR. Pelvic dimensions were measured using three-dimensional reconstruction of computed tomography images. The optimal cutoff value of the pelvic inlet plane area that predicts anastomotic leakage was determined using a receiver operating characteristic (ROC) curve. RESULTS: We observed anastomotic leakage in 10 (8.5%) of the 117 patients. In the multivariate analysis, we identified high body mass index (odds ratio 1.674; 95% confidence interval: 1.087-2.58; P = 0.019) and smaller pelvic inlet plane area (odds ratio 0.998; 95% confidence interval: 0.997-0.999; P = 0.012) as statistically significant risk factors for anastomotic leakage. According to the receiver operating characteristic curves, the optimal cutoff value of the pelvic inlet plane area was 10074 mm2. Narrow pelvic inlet plane area (≤ 10074 mm2) predicted anastomotic leakage with a sensitivity of 90%, a specificity of 85.9%, and an accuracy of 86.3%. CONCLUSION: Narrow pelvic inlet and obesity were independent risk factors for anastomotic leakage after ISR. Anastomotic leakage after ISR may be predicted from a narrow pelvic inlet plane area (≤ 10074 mm2).